Objective: aaWilson’s disease (WD) is a rare genetic disorder of copper metabolism, and longitudinal follow-up studies are limited. We performed a retrospective analysis to determine the clinical characteristics and long-term outcomes in a large WD cohort. Methods: aaMedical records of WD patients diagnosed from 2006–2021 at National Taiwan University Hospital were retrospectively evaluated for clinical presentations, neuroimages, genetic information, and follow-up outcomes. Results: aaThe present study enrolled 123 WD patients (mean follow-up: 11.12 ± 7.41 years), including 74 patients (60.2%) with hepatic features and 49 patients (39.8%) with predominantly neuropsychiatric symptoms. Compared to the hepatic group, the neuropsychiatric group exhibited more Kayser-Fleischer rings (77.6% vs. 41.9%, p < 0.01), lower serum ceruloplasmin levels (4.9 ± 3.9 vs. 6.3 ± 3.9 mg/dL, p < 0.01), smaller total brain and subcortical gray matter volumes (p < 0.0001), and worse functional outcomes during follow-up (p = 0.0003). Among patients with available DNA samples (n = 59), the most common mutations were p.R778L (allelic frequency of 22.03%) followed by p.P992L (11.86%) and p.T935M (9.32%). Patients with at least one allele of p.R778L had a younger onset age (p = 0.04), lower ceruloplasmin levels (p < 0.01), lower serum copper levels (p = 0.03), higher percentage of the hepatic form (p = 0.03), and a better functional outcome during follow-up (p = 0.0012) compared to patients with other genetic variations. Conclusion aaThe distinct clinical characteristics and long-term outcomes of patients in our cohort support the ethnic differences regarding the mutational spectrum and clinical presentations in WD.

Thyroid cancer is the most common endocrine malignancy. Patients with well-differentiated thyroid cancers, such as papillary and follicular cancers, have a favorable prognosis. However, poorly differentiated thyroid cancers, such as medullary, squamous and anaplastic advanced thyroid cancers, are very aggressive and insensitive to radioiodine treatment. Thus, novel therapies that attenuate metastasis are urgently needed. We found that both PDGFC and PDGFRA are predominantly expressed in thyroid cancers and that the survival rate is significantly lower in patients with high PDGFRA expression. This finding indicates the important role of PDGF/PDGFR signaling in thyroid cancer development. Next, we established a SW579 squamous thyroid cancer cell line with 95.6% PDGFRA gene insertion and deletions (indels) through CRISPR/Cas9. Protein and invasion analysis showed a dramatic loss in EMT marker expression and metastatic ability. Furthermore, xenograft tumors derived from PDGFRA geneedited SW579 cells exhibited a minor decrease in tumor growth. However, distant lung metastasis was completely abolished upon PDGFRA gene editing, implying that PDGFRA could be an effective target to inhibit distant metastasis in advanced thyroid cancers. To translate this finding to the clinic, we used the most relevant multikinase inhibitor, imatinib, to inhibit PDGFRA signaling. The results showed that imatinib significantly suppressed cell growth, induced cell cycle arrest and cell death in SW579 cells. Our developed noninvasive apoptosis detection sensor (NIADS) indicated that imatinib induced cell apoptosis through caspase-3 activation. In conclusion, we believe that developing a specific and selective targeted therapy for PDGFRA would effectively suppress PDGFRA-mediated cancer aggressiveness in advanced thyroid cancers.

Thyroid cancer is the most common endocrine malignancy. Patients with well-differentiated thyroid cancers, such as papillary and follicular cancers, have a favorable prognosis. However, poorly differentiated thyroid cancers, such as medullary, squamous and anaplastic advanced thyroid cancers, are very aggressive and insensitive to radioiodine treatment. Thus, novel therapies that attenuate metastasis are urgently needed. We found that both PDGFC and PDGFRA are predominantly expressed in thyroid cancers and that the survival rate is significantly lower in patients with high PDGFRA expression. This finding indicates the important role of PDGF/PDGFR signaling in thyroid cancer development. Next, we established a SW579 squamous thyroid cancer cell line with 95.6% PDGFRA gene insertion and deletions (indels) through CRISPR/Cas9. Protein and invasion analysis showed a dramatic loss in EMT marker expression and metastatic ability. Furthermore, xenograft tumors derived from PDGFRA geneedited SW579 cells exhibited a minor decrease in tumor growth. However, distant lung metastasis was completely abolished upon PDGFRA gene editing, implying that PDGFRA could be an effective target to inhibit distant metastasis in advanced thyroid cancers. To translate this finding to the clinic, we used the most relevant multikinase inhibitor, imatinib, to inhibit PDGFRA signaling. The results showed that imatinib significantly suppressed cell growth, induced cell cycle arrest and cell death in SW579 cells. Our developed noninvasive apoptosis detection sensor (NIADS) indicated that imatinib induced cell apoptosis through caspase-3 activation. In conclusion, we believe that developing a specific and selective targeted therapy for PDGFRA would effectively suppress PDGFRA-mediated cancer aggressiveness in advanced thyroid cancers.

PURPOSE: Single-incision laparoscopic surgery (SILS) is a rapidly evolving technique which bridges traditional laparoscopic surgery and natural orifice transluminal endoscopic surgery (NOTES). We previously published a study comparing single port laparoscopic cholecystectomy (SPLC) and three port laparoscopic cholecystectomy (TPLC). We concluded that age, sex, diagnosis, body mass index (BMI), length of hospital stay, and mobilization between SPLC and TPLC produced no effect on the surgical requirements or outcomes between the two techniques. However, there were significant differences in operating time and pain scale. Thus, in this study we aimed to analyze those factors which reduced operating time. METHODS: This retrospective medical record review enrolled 49 patients who had received SPLC at Presbyterian Medical Center from April 2009 to November 2010. Patient age, sex, BMI, length of hospital stay, operating time, pathological reports, and incidents of iatrogenic gallbladder (GB) perforation and complications were assessed and analyzed. For determining those factors which necessitated long operating times, we assessed the operating times relative to incidents of iatrogenic GB perforation, pathologic report results, surgeon experience and patient BMI. RESULTS: The ratio of men to women in the study population was 1 : 6. The average patient age was 46 years (range of 21 to 93 years). The average BMI was 24.1 (range of 18.5 to 31.5). The mean duration of hospital stay was 5.12 days (range of 2 to 15 days). The average operating time was 118 minutes (range of 75 minutes to 185 minutes). The pathologic report assessments revealed cases of acute calculous cholecystitis (n=4, 8.2%), chronic calculous cholecystitis (n=37, 76.1%) and GB polyp (n=8, 16.3%). Iatrogenic perforation of the GB occurred in 5 cases. Minor complications such as surgical site infection and umbilical skin burn occurred in 6 cases. Longer operating times were required in the GB perforation cases than in the non-perforation cases (155+/-21.21 minutes versus 113.9+/-30.71 minutes, p=0.008). Of the cases of acute and chronic calculous cholecystitis and GB polyp, those including acute calculous cholecystitits required the longest operation times. The average operating time for the first 25 cases was 134.6+/-33.16 minutes and the average operating time for the remainder was 100.8+/-20.41 minutes (p=0.001). There was no significant difference in operating time between the BMI>24 and BMI<24 groups (125.9+/-35.17 minutes versus 111.2+/-27.65 minutes, respectively, p=0.112). CONCLUSION: We found 3 factors related to a reduction in operation time: (i) avoidance of iatrogenic perforation of the GB, (ii) application of treatment to case of chronic calculous cholecystitis and GB polyp, and (iii) accumulation of case experience by the attending surgeon.
Body Mass Index ; Burns ; Cholecystectomy, Laparoscopic ; Cholecystitis ; Female ; Gallbladder ; Humans ; Laparoscopy ; Length of Stay ; Male ; Medical Records ; Natural Orifice Endoscopic Surgery ; Operative Time ; Polyps ; Protestantism ; Retrospective Studies ; Skin

Pseudomembranous colitis is mainly caused by antibiotics and Clostridium difficile infection. But conditions such as gastrointestinal surgery, antacid medication, anti-neoplastic agent or immunosuppressive agent which influences the normal flora of colon can induce colitis without the administration of any antibiotics. We experienced a 13 year-old male who was taking low-dose methotrexate for juvenile rheumatoid arthritis complained diarrhea and abdominal pain for 3 weeks. Sigmoidoscopic findings revealed diffuse patch yellowish pseudomembranes on the rectum. Histologic finding was compatible to pseudomembranous colitis. His symptom was improved after stop taking methotrexate and the administration of metronidazole. If a patient treated with immunosuppressive agents or antineoplastic agents complains diarrhea, fever or abdominal pain and has not improved with conservative care, pseudomembranous colitis should be taken into account as a differential diagnosis and prompt treatment is required for better prognosis.
Abdominal Pain/etiology ; Adolescent ; Anti-Infective Agents/therapeutic use ; Antirheumatic Agents/*adverse effects/therapeutic use ; Arthritis, Juvenile Rheumatoid/*drug therapy ; Diagnosis, Differential ; Diarrhea/etiology ; Enterocolitis, Pseudomembranous/*diagnosis/drug therapy/pathology ; Humans ; Male ; Methotrexate/*adverse effects/therapeutic use ; Metronidazole/therapeutic use ; Sigmoidoscopy ; Tomography, X-Ray Computed

This study investigated the experience and practice of elementary school students on nutrition education. The data were collected from 217 male and female students attending 5-6th grade elementary schools in Seoul and Kyunggi-Do from March to June 2007, interviewing face to face by a nutrition teacher and 3 interns of a nutrition teacher. The results were as follows: 86.5% of the subjects learned about 'Table etiquette', 'Reasons for eating fruits and vegetables'(78.7%), 'Food waste and environment'(72.3%), 'Healthy snacks'(55.7%), 'Food sanitation'(52.3%), 'Food culture of foreign countries'(48.1%). Nutrition education experience was significantly different by gender. A total of 43.5% boys responded that they never learned about 'basic food preperation'(p < 0.01). They had learned 'Nutrients for body'and 'Food waste and environment'in school, 'Healthy weight loss', 'Food culture of foreign countries', 'Food circulation'on television, Most content ('Table etiquette', 'Simple cooking', 'Food sanitation', 'Eating behaviors for health', 'Reasons for eating fruits and vegetables', 'Healthy snacks') was learned from parents. The practice after nutrition education was higher in 'Table etiquette'(2.14), 'Eating fruits and vegetables'(2.07) than others compared with education experience. The most reason of non-practice on nutrition information was 'Troublesome'. In 'Nutrients for body', a boy answered 'Difficult for practice'20.0%, a girl answered 'Difficult to understand'32.6%, showing a significant difference between the gender groups (p < 0.001). They remembered the 'Nutrients for body'(49.6%), 'Food sanitation'(44.5%) because of 'important content', 'Basic food preparation'(40.6%), 'Food culture of foreign countries'(36.3%) because of 'interesting content', 'Healthy weight loss'(52.0%), 'Eating behavior for health'(44.5%) and 'Healthy snacks'(33.7%) because of 'need for my health'.
Eating ; Female ; Fruit ; Humans ; Male ; Parents ; Television